Johnson & Johnson: CHMP recommends TECVAYLI plus daratumumab for relapsed/refractory multiple myeloma
- EMA CHMP recommended an indication extension for teclistamab (TECVAYLI) in combination with daratumumab for adults with relapsed/refractory multiple myeloma after at least one prior therapy.
- Phase 3 MajesTEC-3 (n=291 vs 296) reported an 83.4% reduction in risk of progression or death with the combination versus standard care (PFS HR 0.17; 95% CI 0.12–0.23).
- Overall survival favoured the combination (OS HR 0.46; 95% CI 0.32–0.65), with three‑year OS rates of 83.3% for the combination versus 65.0% for standard of care.
- Safety was consistent with known profiles: all cytokine release syndrome events were Grade 1/2 and manageable; Grade 3/4 TEAEs were similar between arms (95.1% vs 96.6%), and discontinuations due to TEAEs were low (4.6% vs 5.5%).
Regulatory recommendation
The EMA Committee for Medicinal Products for Human Use (CHMP) has recommended approval of an indication extension for teclistamab (TECVAYLI) in combination with daratumumab for adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
Phase 3 efficacy
The CHMP opinion is supported by MajesTEC-3 data. At nearly three years’ follow-up the teclistamab plus daratumumab subcutaneous combination reduced the risk of disease progression or death by 83.4% versus investigator’s choice standard regimens (PFS HR 0.17; 95% CI 0.12–0.23; p<0.0001). More than 90% of patients progression‑free at six months (n=249) remained progression‑free at three years. Overall survival also favoured the combination (OS HR 0.46; 95% CI 0.32–0.65; p<0.0001), with three‑year OS rates of 83.3% versus 65.0% and benefit observed across prespecified subgroups.
Safety
Safety was consistent with the known profiles of the individual agents. All cytokine release syndrome events were Grade 1/2, manageable, and did not lead to discontinuation. Grade 3/4 treatment‑emergent adverse events were comparable between arms (95.1% vs 96.6%), with cytopenias and infections most common. Grade ≥3 infections decreased over time with immunoglobulin supplementation, infection prophylaxis and a switch to monthly dosing; discontinuations for TEAEs were low (4.6% vs 5.5%).
Study design and context
MajesTEC-3 is an ongoing Phase 3 randomised study comparing teclistamab plus daratumumab SC (n=291) versus investigator’s choice daratumumab SC plus dexamethasone with either pomalidomide or bortezomib (n=296) in patients with 1–3 prior lines. The primary endpoint is progression‑free survival; secondary endpoints include depth of response (≥CR), ORR, MRD negativity (10⁻⁵ by NGS), overall survival and patient‑reported symptom worsening (MySIm‑Q).
Source: J&J
